Migraine is a common condition, while migraine headache is a chronic condition, prophylactic and symptomatic treatments are available. In particular, the development of selective serotonin agonists such as triptans has been a tremendous breakthrough in the treatment of migraine headaches. Zolmitriptan is one of them and is a selective 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist, which is known as (S)-4-[[3-[2-(Dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone and its chemical structure is shown in the following Formula I.

Zolmitriptan is available for oral administration in conventional and orally disintegrating tablet formulations and indicated for the acute treatment of migraine. Orally disintegrating tablets are available as Zomig-ZMT™ containing 2.5 mg or 5.0 mg zolmitriptan as active ingredient; and mannitol, microcrystalline cellulose, crospovidone, aspartame, sodium bicarbonate, citric acid anhydrous, colloidal silicon dioxide, magnesium stearate and flavor as excipients.
Various formulations and methods are already known for the preparation of orally disintegrating formulations. However, orally disintegrating formulations are becoming an increasingly important issue in the area of better patient compliance as compared to conventional solid dosage forms for oral administration, such as capsules and tablets. In particular, pediatric and geriatric patients frequently have difficulty in swallowing conventional solid dosage forms. In addition, for many medicaments, the act of swallowing the medicament often requires fluids that increase gastric volume and the likelihood of nausea and vomiting. This occurs more often in migraine patients. Perhaps the biggest advantage of orally disintegrating dosage forms is that the solid dosage form dissolves or disintegrates quickly in the oral cavity, resulting in a solution or suspension without the need for the administration of fluid. Accordingly, the patient can administer the dosage form as soon as symptoms are felt. Thus, the orally disintegrating dosage form is one of the advantageous methods to deliver the drugs such as those comprising zolmitriptan to such patients and provide a better patient compliance with recommended pharmaceutical therapies.
In addition, by administering the orally disintegrating dosage forms, faster absorption of the drug occurs through buccal mucosa and it may reduce the first pass metabolism leading to better efficacy of the drug. This dosage form enhances the clinical effects of some drugs by leading to an increase in bioavailability and a reduction in side effects because of avoidance of first-pass liver metabolism.
It is known that the development of orally disintegrating compositions are difficult for several different reasons. A satisfied orally disintegrating dosage form needs to meet number of requirements. Firstly, it has to disintegrate in the oral cavity rapidly. Moreover, a premature release in the mouth could also lead to problems due to the often unpleasant taste of the active ingredient. Besides, these compositions should be very porous and should not be very hard. These porous compositions tend to be very sensitive to humidity. As a consequence, they may have some stability problems. Finally, any orally disintegrating composition with suitable organoleptic and pharmacokinetic properties must also be manufactured at commercially useful rates and yields and using more simple methods.
To fulfill all these requirements, the formulation for a specific drug needs to be adapted in particular by a careful selection of the excipients used. However, the excipients selected may lead to formulations which are not bioavailable to the corresponding conventional dosage forms. Thus, they have to be chosen very carefully. Additionally, precautions have to be taken in the preparation, packaging, handling and storing of the finished dosage forms of orally disintegrating compositions since they tend to be both hygroscopic and friable.
Thus, various technologies have been developed which enable the preparation of compositions that disintegrate quickly in the oral cavity. These technologies include spray drying, freeze drying and floss formation. However, all of these technologies have their own limitations.
The spray drying technique involves spraying the drug and excipients into a chamber maintained at a high temperature. As a result, this technique is not suitable for application to thermo-labile drugs. Additionally, spray drying technology leads only to very poor output and is very expensive.
Freeze drying on a large scale has not been found to be very effective. Moreover, it has limitations due to factors such as time, costly equipment and processing conditions. In addition, the Zydis® tablets prepared by this technique are so fragile that the formation of the matrix material has to take place in a specific container. Tablets manufactured by this technology require a special type of packaging and careful handling during dispensing and administration to the patients, since they are prone to breakage. For example, EP 1 246 668 B1, relates to a fast acting oral pharmaceutical composition and particularly relates to fast-acting, freeze-dried pharmaceutical composition of zolmitriptan.
The floss formation technique includes compressing micro-particles of a drug and a cotton candy-like fibrous saccharide matrix, such as sucrose, dextrose, lactose and fructose. This technique is also known as Flash Dose technology (Fuisz) and requires specific equipment for making the specific matrix, which is sensitive to moisture, and generally results in tablets of high friability.
Finally, many of these techniques have proved to be only successful for specific drugs. These techniques are often not transferable to other active ingredients or may cause additional problems.
Thus, a need rises for orally disintegrating tablet formulations of zolmitriptan or a pharmaceutically acceptable salt thereof and a process for preparing such formulation which overcomes the above described problems in the prior art and having added advantages over them. Further advantages and embodiments of the present invention will become apparent from the following description.